Abstract
Cancer chemotherapy often results in side effects
such as high toxicity and drug resistance. Sequential
and simultaneous delivery of drug combinations have been
found to reduce the side effects associated with systemic
delivery of anticancer drugs. An alternative approach to
systemic delivery of anticancer drugs is the co-conjugation
of two or more of these agents to a single polymeric carrier
via biofissionable linkages. In this study, macromolecular
co-conjugates of bisphosphonate and ferrocene were synthesized
and the kinetic drug release studied. Phosphorus
and proton NMR and FTIR were used to characterize the
co-conjugates. The mass percentages incorporation of ferrocene
analogue were found to be between 4–5 % and
10–12 % for bisphosphonate. Kinetic drug release results
at selected pH (1.2, 5.5 and 7.4) were fitted in different
mathematical drug release model to determine the
mechanism of release of ferrocene and bisphosphonate
from a co-conjugate pro-drug. The best model describing
the release of ferrocene were found to be Korsmeyer–
Peppas model at pH 1.2 and zero order model at pH 5.5 and
7.4. For bisphosphonate, Korsmeyer–Peppas, Higuchi and
zero order models were found to best fit the release
mechanism at pH 1.2, 5.5 and 7.4 respectively.